aUniversity of Arkansas, Little Rock, Arkansas bUniversity of Michigan, Ann Arbor, Michigan, USA.
Curr Opin Rheumatol. 2014 Mar;26(2):204-10. doi: 10.1097/BOR.0000000000000036.
T lymphocytes are critical to the pathogenesis of systemic rheumatic diseases. Understanding of the roles of T cells in disease has been enriched by the description of highly distinct effector subsets of CD4 T lymphocytes. The purpose of this review is to describe selected advances in the biology of T lymphocytes that are pertinent to the pathogenesis or treatment of rheumatic diseases.
Knowledge is expanding about not only pathogenic effector T cell subsets, such as the TH17 cells, but also of regulatory T cells (Treg), the functions of which are defective, but correctable, in several rheumatic diseases. Although the initial agent that demonstrated a role for T cells in rheumatoid arthritis was CTLA4-Ig (abatacept), use of this biologic is now expanding to other rheumatic diseases. Moreover, effects of other biologics are now understood to in part be mediated by effects on T cell subsets. Experimental model systems in rodents continue to be valuable testing grounds for future approaches to treatment of human disease. Meanwhile, the roles of effector T cell subsets are becoming clearer in conditions such as Sjogren's syndrome and scleroderma. Finally, rheumatic diseases, including rheumatoid arthritis and spondyloarthropathies, have been critical for identification of new innate-like T cell subsets.
Imbalances in the numbers and functions of specific T cell subsets are key pathogenic derangements in systemic rheumatic diseases, and these insights are leading to changes in clinical practice.
T 淋巴细胞对于系统性风湿性疾病的发病机制至关重要。通过描述高度独特的 CD4 T 淋巴细胞效应亚群,人们对 T 细胞在疾病中的作用有了更深入的了解。本文的目的是描述与风湿性疾病的发病机制或治疗相关的 T 淋巴细胞生物学方面的一些选定进展。
人们不仅对致病性效应 T 细胞亚群(如 TH17 细胞)有了更多的了解,而且对调节性 T 细胞(Treg)也有了更多的了解,在几种风湿性疾病中,Treg 的功能存在缺陷,但可以纠正。尽管最初证明 T 细胞在类风湿关节炎中起作用的药物是 CTLA4-Ig(阿巴西普),但现在这种生物制剂的应用范围已经扩大到其他风湿性疾病。此外,其他生物制剂的作用现在被认为部分是通过对 T 细胞亚群的影响来介导的。啮齿动物的实验模型系统仍然是研究人类疾病治疗未来方法的宝贵试验场。同时,效应 T 细胞亚群在干燥综合征和硬皮病等疾病中的作用也越来越明确。最后,风湿性疾病,包括类风湿关节炎和脊柱关节病,对于鉴定新的固有样 T 细胞亚群至关重要。
特定 T 细胞亚群数量和功能的失衡是系统性风湿性疾病的关键发病机制紊乱,这些新发现正在改变临床实践。